METABOLISM OF [3-C-13]PYRUVATE AND [3-C-13]PROPIONATE IN NORMAL AND ISCHAEMIC RAT HEART IN VIVO - H-1- AND C-13-NMR STUDIES

摘要

The oxidation of ?3-C-13?pyruvate and ?3-C-13?propionate was studied in vivo in infused rats. The infused ?3-C-13?pyruvate was quickly converted to ?3-C-13?lactate in the blood, and the ?3-C-13?lactate formed was well metabolized in both normoxic and ischaemic hearts. Large differences (200-600%) in the C-13 enrichment of alanine (C-3) and acetyl-CoA (C-2) compared with lactate (C-3) were found in both normoxic and ischaemic hearts, suggesting that the extracellular ?3-C-13?lactate preferentially entered a region of the cytoplasm which specifically transfers the labelled pyruvate (formed from ?3-C-13?lactate) to the mitochondria. The highly enriched mitochondrial pyruvate gave high enrichment in alanine and acetyl-CoA, which was detected by H-1- and C-13-NMR spectroscopy. Ischaemia increased C-13 incorporation into the main cytoplasmic lactate pool and decreased C-13 incorporation into citric acid cycle intermediates, mainly decreasing the pyruvate anaplerosis. Isoprenaline-induced ischaemia of the heart caused only a slight decrease in pyruvate oxidation. In contrast to the decreased anaplerosis of pyruvate, the anaplerosis of propionate (and propionyl-carnitine) increased significantly in ischaemic hearts, which may contribute to the protective effect of propionyl-carnitine seen in ischaemia. In addition, we found that ?3-C-13?propionate preferentially labelled aspartate C-3 in rat heart, suggesting incomplete randomization of label in the succinyl-CoA-malate span of the citric acid cycle. These data show that proton observed C-13 edited spectroscopic methods, i.e. heteronuclear spin-echo and the one-dimensional heteronuclear multiple quantum coherence sequence, can be successfully used to study heart metabolism in vivo. [References: 33]